Editing Proton-pump inhibitor (section)

== Mechanism of action ==
[[File:Proton pump inhibitors mechanism.svg|thumb|upright=1.3|class=skin-invert-image|The activation of PPIs]]
[[Proton pump]] inhibitors act by irreversibly blocking the [[hydrogen]]/[[potassium]] [[ATPase|adenosine triphosphatase]] [[enzyme]] system (the [[Hydrogen potassium ATPase|H<sup>+</sup>/K<sup>+</sup> ATPase]], or, more commonly, the gastric proton pump) of the gastric [[parietal cells]].<ref>{{cite book | vauthors = Sakai H, Fujii T, Takeguchi N |publisher= Springer|date= 2016|series= Metal Ions in Life Sciences|volume=16|title=  The Alkali Metal Ions: Their Role in Life| veditors = Astrid S, Helmut S, Roland SK |chapter= Chapter 13. Proton-Potassium (H+/K+) ATPases: Properties and Roles in Health and Diseases|pages= 459–483|doi=10.1007/978-3-319-21756-7_13|pmid= 26860309|isbn= 978-3-319-21755-0}}</ref> The proton pump is the terminal stage in gastric acid secretion, being directly responsible for secreting H<sup>+</sup> ions into the gastric lumen, making it an ideal target for inhibiting acid secretion.{{citation needed|date=May 2022}} Because the H,K-ATPase is the final step of acid secretion, an inhibitor of this enzyme is more effective than receptor antagonists in suppressing gastric acid secretion.<ref>{{cite journal |last1=Fellenius |first1=Erik |last2=Berglindh |first2=Thomas |last3=Sachs |first3=George |last4=Olbe |first4=Lars |last5=Elander |first5=Berit |last6=Sjöstrand |first6=Sven-Erik |last7=Wallmark |first7=Björn |date=March 1981 |title=Substituted benzimidazoles inhibit gastric acid secretion by blocking (H+ + K+) ATPase |url=http://dx.doi.org/10.1038/290159a0 |journal=Nature |volume=290 |issue=5802 |pages=159–161 |doi=10.1038/290159a0 |pmid=6259537 |bibcode=1981Natur.290..159F |s2cid=4368190 |issn=0028-0836}}</ref> All of these drugs inhibit the gastric H,K-ATPase by covalent binding, so the duration of their effect is longer than expected from their levels in the blood.<ref>{{cite journal |last1=Shin |first1=Jai Moo |last2=Sachs |first2=George |date=November 2002 |title=Restoration of acid secretion following treatment with proton pump inhibitors |journal=Gastroenterology |volume=123 |issue=5 |pages=1588–1597 |doi=10.1053/gast.2002.36593 |pmid=12404233 |issn=0016-5085|doi-access=free }}</ref>

Targeting the terminal step in acid production, as well as the [[Irreversible inhibitor|irreversible]] nature of the inhibition, results in a class of medications that are significantly more effective than [[H2 antagonist|H<sub>2</sub> antagonists]] and reduce gastric acid secretion by up to 99%.<ref name="pmid16700898">{{cite journal | vauthors = Sachs G, Shin JM, Howden CW | title = Review article: the clinical pharmacology of proton pump inhibitors | journal = Alimentary Pharmacology & Therapeutics | volume = 23 | issue = Suppl 2 | pages = 2–8 | date = June 2006 | pmid = 16700898 | doi = 10.1111/j.1365-2036.2006.02943.x | s2cid = 30413194 | doi-access = free }}</ref>

Decreasing the acid in the stomach can aid the healing of [[duodenum|duodenal]] ulcers and reduce the pain from indigestion and [[heartburn]]. However, [[stomach acid]]s are needed to digest proteins, [[Vitamin B12|vitamin B<sub>12</sub>]], calcium, and other nutrients, and too little stomach acid causes the condition [[hypochlorhydria]].{{citation needed|date=May 2022}}

The PPIs are given in an inactive form, which is neutrally charged ([[lipophilic]]) and readily crosses [[cell membrane]]s into intracellular compartments (like the parietal cell canaliculus) with acidic environments. In an acid environment, the inactive drug is protonated and rearranges into its active form. As described above, the active form will [[covalent]]ly and irreversibly bind to the gastric proton pump, deactivating it.

In [[Helicobacter pylori eradication protocols|''H. pylori'' eradication]], PPIs help by increasing the stomach pH, causing the bacterium to shift out of its coccoid form which is resistant to both acids and antibiotics. PPIs also show some weaker additional effects in eradication.<ref name="pmid31558859">{{cite journal | vauthors = Ierardi E, Losurdo G, Fortezza RF, Principi M, Barone M, Leo AD | title = Optimizing proton pump inhibitors in Helicobacter pylori treatment: Old and new tricks to improve effectiveness | journal = World J Gastroenterol | volume = 25 | issue = 34 | pages = 5097–5104 | date = September 2019 | pmid = 31558859 | pmc = 6747288 | doi = 10.3748/wjg.v25.i34.5097 | doi-access = free }}</ref>